Introduction: The heterozygous activating mutations in the KCNJ11 and ABCC8 are the commonest causes of permanent neonatal diabetes mellitus (PNDM). The most severe clinical form of NDM is DEND syndrome. Besides diabetes mellitus such patients show severe developmental delay, hypotonia and therapy-resistant epilepsy. To our knowledge only some cases of DEND syndrome due to ABCC8 mutations are sulfonylurea-responsive. Here we report case of DEND syndrome due to F132L ABCC8 mutation who was completely switched from insulin to sulfonylurea monotherapy.
Clinical case: A boy was born as a first child of non-consanguineous parents following an uneventful pregnancy and spontaneous term delivery. His birthweight was 2830 g (−1.77 SDS). At 3 month of age he presented with failure to thrive, hyperglycemia (18 mmol/l), ketosis, severe hypotonia and frequent generalized clonic-tonic seizures unresponsive to increasing doses of the anti-epileptic drugs (phenobarbital, valproic acid, levetiracetam, vigabatrin). NDM was diagnosed and continuous subcutaneous insulin pump therapy was started. At 5 month of age he was referred to our hospital because of ongoing seizures and poor glycemic control (HbA1c was 10.5%). Also he had hypotonia and severe developmental delay. Most of the time he spent lying on his back, did not hold his head and did not roll over. He could not babble and was not interested in toys. De novo heterozygous mutation F132L in ABBC8 gene was identified. After genetic testing the patient was successfully transferred to glibenclamide at a daily dose of 0.4 mg/kg. Now he is 1 year and 6 months old. His HbA1c decreased to 5.7%. The glibenclamide dose remained unchanged (0.4 mg/kg per day). During period of observation we have not seen any side effects, including severe hypoglycemia. Also we have noticed an improvement in his neurological status. He does not have seizures and sings of hypsarrhythmia according to EEG. His tone is also improved so he is able to hold his head, roll over and sit with support.
Conclusion: Any patient with NDM should be genetically tested and then referred to a tertiary center with experience of NDM management. The F132L/ABCC8 mutation seems to have a chance of positive response to glibenclamide monotherapy in doses around 0.4 mg/kg per day with improvement of neurological symptoms.
27 Sep 2018 - 29 Sep 2018